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Folic acid was coupled to melphalan using glycyl-glycine (FA-Gly-Gly-Melphalan) to synthesise self-assembled nanomicelles for targeting ovarian cancer cells, SKOV3.FA-Gly-Gly-Melphalan self-assembled nanomicelles were prepared with critical micellar concentration (CMC) of 12-μg/ml. The mean particle size of FA-Gly-Gly-Melphalan self-assembled nanomicelles was measured to be 95.9 ± 3.4-nm significantly (FA-Gly-Gly-Melphalan self-assembled nanomicelles warrant in depth

Ischemic stroke is characterized by the presence of both brain ischemic and reperfusion-induced injuries in the brain, leading to neuronal dysfunction and death. Artemisinin, an FDA-approved antimalarial drug, has been reported to have neuroprotective properties. However, the effect of artemisinin on ischemic stroke is not known. In the present study, we investigated the effect of artemisinin on ischemic stroke using an oxygen-glucose deprivation/reperfusion (OGD/RP) cellular model and a mouse middle cerebral artery occlusion (MCAO) animal model and examined the underlying mechanisms. The obtained results revealed that a subclinical antimalarial concentration of artemisinin increased cell viability and decreased LDH release and cell apoptosis. Artemisinin also attenuated the production of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (Δψm). Importantly, artemisinin attenuated the infarction volume and the brain water content in the MCAO animal model. Artemisinin also improved neurological and behavioural outcomes and restored grasp strength and the recovery of motor function in MCAO animals. Furthermore, artemisinin treatment significantly inhibited the molecular indices of apoptosis, oxidative stress and neuroinflammation and activated the ERK1/2/CREB/BCL-2 signaling pathway. Further validation of the involved signaling pathway by the ERK1/2 inhibitor PD98059 revealed that inhibiting the ERK1/2 signaling pathway or silencing ERK1/2 reversed the neuroprotective effects of artemisinin. These results indicate that artemisinin provides neuroprotection against ischemic stroke via the ERK1/2/CREB/BCL-2 signaling pathway. Our study suggests that artemisinin may play an important role in the prevention and treatment of stroke.

Hu Zhou,1,2,* Yuan Yuan,1– 3,* Haorun Wang,1,2 Wei Xiang,1,2 shenjie Li,1,2 Haowen Zheng,1,2 Yuqi Wen,1,2 Yang Ming,1,2 Ligang Chen,1,2,4,5 Jie Zhou1,2,4,5 1Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People’s Republic of China; 3Department of Operation and Anaesthesia, Yibin First People’s Hospital, Yibin, Sichuan, People’s Republic of China; 4Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 5Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Zhou Email zj000718@yeah.netAbstract: The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.Keywords: intestinal flora, carcinogenesis, mechanism, therapy, fecal bacteria transplantation

Background：Matrix stiffness in tumor microenvironment is tightly correlated with the tumor progression in solid cancer. However, the potential role of matrix stiffness in glioma progression remains controversial. Our study aimed to explore the underlying mechanism of glioma progression induced by matrix stiffness. Methods: Atomic force microscopy analysis was performed to examine the stiffness of tumor tissues. tunable polyacrylamide (PA) hydrogels were used for cells culture with different matrix stiffness. CCK-8 analysis was used to examine the cells proliferation. Colony formation analysis and subcutaneous tumor-bearing mice model were used to detect the capability of tumorigenesis. Western blotting and immunofluorescent staining were performed to examine the signals activation in glioma cells. Results: In our study, we observed a higher matrix stiffness in high degree glioma tissues from patients. We demonstrated that a higher stiffness culture system could mediate the upregulation of stemness in glioma cells, resulting in the strengthen capability of tumor growth and relapse in glioma. In mechanism, we observed activation of integrin α5β1/JAK1/STAT3/c-Myc signaling pathway in glioma cells under the simulation of a higher matrix stiffness. Combination of STAT3 inhibitor STAT3-IN-1 and chemotherapeutic temozolomide (TMZ) obviously suppressed the xenogenous glioma mice model, which revealed strengthen anticancer effects and improved outcome.Conclusion: We demonstrated that a higher matrix stiffness could promote glioma progression through an integrin α5β1/JAK1/STAT3/c-Myc signaling pathway. Blockade of STAT3 signals improved the anticancer effects of chemotherapy, providing new insights for glioma therapy in clinic.

With the rapid development of China’s economy and the increasing level of urbanization, more and more attention has been paid to urban air pollution. Accurate monitoring of air quality at high altitude is always a problem. It is difficult to collect air quality data at high altitude, and the high cost leads to the lack of data collection of air quality at vertical height. It is imperative to combine UAV and traditional environmental monitoring devices to learn from each other when it is necessary to periodically test and compare air quality data at different altitudes. Environment monitoring system based on UAV, environment monitoring device and Internet. The system includes four rotor UAV, environmental monitoring terminal and computer environmental monitoring platform. This paper mainly studies and designs from these three parts.

Additional file 1: Supplementary Table 1. Patient background and molecular status. Supplementary Table 2. Patient background of four molecular groups divided by the combined IDH/TERT status in WHO II-IV diffuse glioma. Supplementary Table 3. Comparisons of perfusion parameters in the four molecular groups divided by the combined MGMT/TERT status in GBM.

With electricity as the main power energy, the UAV has been affected by the impact of battery storage on the flight time and flight time, which makes the UAV need to constantly replace the battery to ensure the long-term operation. The automatic endurance system takes the remaining power of the UAV as the independent variable, and the average value of the flight data of the UAV battery for nearly three times as the judgment basis. It realizes the automatic navigation in the UAV area, charges the base station after landing accurately, and improves the endurance time of the UAV.

Yu Xiong,1– 3,* Xue Lai,4,* Wei Xiang,1– 3 Jie Zhou,1– 3 Jizhong Han,1– 3 Hao Li,1– 3 Huajiang Deng,1– 3 Luotong Liu,1– 3 Jianhua Peng,1– 3 Ligang Chen1– 3 1Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Neurosurgery Clinical Medical Research Center of Sichuan Province, Luzhou 646000 People’s Republic of China ; 3Academician (Expert) Workstation of Sichuan Province; 4Day Surgery Center, Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ligang ChenDepartment of Neurosurgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000, People’s Republic of ChinaTel +86 138 82718881Email chengligang.cool@163.comBackground: Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCFSkp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway.Methods: CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN.Results: GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay.Conclusion: This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.Keywords: galangin, GBM, EMT, Skp2, ubiquitination

Objective: This meta-analysis assessed the long-term efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) for Parkinson disease (PD). Methods: PubMed, Cochrane Library, and Clinical Trials databases were searched. Outcomes were unified Parkinson disease rating scale section (UPDRS) III off-medication score, Parkinson's disease questionnaire: 39 activities of daily living (PDQ-39 ADL) score, and levodopa-equivalent dosage after DBS. Results: During the off-medication state, pooled weighted mean difference (WMD) of UPDRS III score was .69 (95% confidence interval [CI] = −1.77 to 3.16, P = .58). In subgroup analysis, WMD of UPDRS III off-medication scores from baseline to 2 years and 3 years post-DBS were −.61 (95% CI = −2.97 to 1.75, P = .61) and 2.59 (95% CI = −2.30 to 7.47, P = .30). Pooled WMD of changes in tremor, rigidity, and gait scores were 1.12 (95% CI = −0.05 to 2.28, P = .06), 1.22 (95% CI = −0.51 to 2.94, P = .17) and .37 (95% CI = −0.13 to 0.87, P = .15), respectively. After DBS, pooled WMD of PDQ-39 ADL and LED were −3.36 (95% CI = −6.36 to −0.36, P = .03) and 194.89 (95% CI = 113.16 to 276.63, P

Pork quality is an economically important trait and one of the main selection criteria for breeding in the swine industry. In this genome-wide association study (GWAS), 455 pigs from a porcine Large White × Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for intramuscular fat content (IMF), marbling, moisture, color L*, color a*, color b* and color score in the longissimus muscle (LM). Association tests between each trait and the SNPs were performed via the Genome Wide Rapid Association using the Mixed Model and Regression-Genomic Control (GRAMMAR-GC) approach. From the Ensembl porcine database, SNP annotation was implemented using Sus scrofa Build 9. A total of 45 SNPs showed significant association with one or multiple meat quality traits. Of the 45 SNPs, 36 were located on SSC12. These significantly associated SNPs aligned to or were in close approximation to previously reported quantitative trait loci (QTL) and some were located within introns of previously reported candidate genes. Two haplotype blocks ASGA0100525-ASGA0055225-ALGA0067099-MARC0004712-DIAS0000861, and ASGA0085522-H3GA0056170 were detected in the significant region. The first block contained the genes MYH1, MYH2 and MYH4. A SNP (ASGA0094812) within an intron of the USP43 gene was significantly associated with five meat quality traits. The present results effectively narrowed down the associated regions compared to previous QTL studies and revealed haplotypes and candidate genes on SSC12 for meat quality traits in pigs.

When the disaster approaches,such as earthquake, landslide, nuclear radiation zone, harsh environment and so on, rescuers can not access to it easily, to solve this,we designed the robot, the robot has six legs, each leg has three free degrees(1). We adopted the embedded system and servo controller as the core controllers,embedded system controller communicates with the servo controller.It realized the human-computer interaction freely by the core controllers combined with voice recognition module, it entered the accident scene freely because of flexible and small size, it communicated with mobile terminal or computer easily because of the unique HD network camera, it searched environment and transmitted the data to the terminal, it searched the target quickly. So it completes the search and rescue mission accurately and effectively, to save time for rescue, so this robot has a very important significance and practical value in the field of various fields(2).

Through activating specific transcriptional programmes, plants can launch resistance mechanisms to stressful environments and acquire a new equilibrium between development and defence. To screen the rice WRKY transcription factor which functions in abiotic stress tolerance and modulates the abscisic acid (ABA) response, we generated a whole array of 35S-OsWRKY transgenic Arabidopsis. In this study, we report that 35S-OsWRKY72 transgenic Arabidopsis, whose seed germination was retarded under normal conditions, emerged more sensitive to mannitol, NaCl, ABA stresses and sugar starvation than vector plants. Meanwhile, 35S-OsWRKY72 transgenic Arabidopsis displayed early flowering, reduced apical dominance, lost high temperature-induced hypocotyl elongation response, and enhanced gravitropism response, which were similar to the auxin-related gene mutants aux1, axr1 and bud1. Further, semi-quantitative RT-PCR showed that the expression patterns of three auxin-related genes AUX1, AXR1 and BUD1 were significantly altered in rosette leaves and infl orescences of 35S-OsWRKY72 plants compared with control Arabidopsis, and two ABA-related genes ABA2 and ABI4 were induced in 35S-OsWRKY72 seedlings. In addition, northern blot analysis indicated that, in rice, OsWRKY72 was inducible by polyethylene glycol (PEG), NaCl, naphthalene acetic acid (NAA), ABA and 42 degrees C, similar to its orthologue AtWRKY75 in Arabidopsis, implying that these two WRKY genes might be required for multiple physiological processes in their plants. Together, these results suggest that OsWRKY72 interferes in the signal cross-talk between the ABA signal and auxin transport pathway in transgenic Arabidopsis.

The new type of real-time robot controller, GKD-1 RRC, designed for robot force/position hybrid control is based on a multilevel bus mode MIMD tightly-coupled multiprocessor structure which can dynamically distribute load to maintain dynamic load balance by the management of the kernel of multiprocessor concurrent operation system and can meet the need of task-based parallel processing. The paper presents the hardware and software structure of the robot controller and its main features. Then some typical experiments on force/position hybrid control schemes and their results are explained. The experimental results show that computer structure of GKD-1 RRC is efficient and applicable, with 4.88 ms force/ position hybrid control cycle, less than 100 gram average force control steady state error, and the accuracy of the position control is same as the original accuracy of the manipulator. >